Fei Ma1, Quchang Ouyang2, Wei Li3, Zefei Jiang4, Zhongsheng Tong5, Yunjiang Liu6, Huiping Li7, Shiying Yu8, Jifeng Feng9, Shusen Wang10, Xichun Hu11, Jianjun Zou12, Xiaoyu Zhu12, Binghe Xu1. 1. National Cancer Center, State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. 2. Hunan Cancer Hospital, Changsha, People's Republic of China. 3. First Affiliated Hospital, Jilin University, Changchun, People's Republic of China. 4. The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China. 5. Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. 6. Cancer Center of Hebei Province and The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China. 7. Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. 8. Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China. 9. Jiangsu Cancer Hospital, Nanjing, People's Republic of China. 10. Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. 11. Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. 12. Jiangsu Hengrui Medicine, Shanghai, People's Republic of China.
Abstract
PURPOSE: Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study. PATIENTS AND METHODS: Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated withtaxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS:Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P < .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively. CONCLUSION: In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.
RCT Entities:
PURPOSE:Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with humanepidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study. PATIENTS AND METHODS: Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS: Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P < .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively. CONCLUSION: In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.
Authors: Maria Mitsogianni; Ioannis P Trontzas; Georgia Gomatou; Stephanie Ioannou; Nikolaos K Syrigos; Elias A Kotteas Journal: Oncol Lett Date: 2021-02-12 Impact factor: 2.967